This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. The main goal of this proposal is to generate important new insights concerning feasibility, efficacy and safety of novel reproductive options designed to minimize the occurrence of mitochondrial (mt) DNA defects in a clinically relevant nonhuman primate model. Our main hypothesis is that mtDNA can be efficiently replaced by a novel approach, i.e., chromosome transfer in mature metaphase II (MII) oocytes without interfering with subsequent nucleo-mtDNA compatibility and developmental competence. Our recent studies demonstrate the feasibility and efficacy of this approach in the rhesus monkey. We showed that reconstructed oocytes produced after chromosome transfer are nearly homoplasmic, capable of supporting normal fertilization and competent for full term development of macaque infants.